Methods for Cancer Prognosis

Abstract

A method for assessing prognosis in a subject having a breast tumor comprises determining the level of expression of at least one Notch receptor gene, Notch ligand gene or Notch signaling target gene. A method of treating a subject suffering from a breast tumor associated with increased Notch signaling comprises administering to the subject an effective amount of an inhibitor of Notch signaling.

1 . A method for assessing prognosis for a subject having a breast tumor, comprising determining the level of expression of at least one Notch receptor gene, Notch ligand gene or Notch signaling target gene in the tumor. 
     
     
         2 . The method of  claim 1  comprising determining the level of expression of at least one gene selected from the group consisting of Notch 1. Notch 3, Jagged 1, Hey 1, Hey 2, HevL, Hes 1, Hes 2, Hes 3, Hes 4. Hes 5, Hes 6 and Hes 7. 
     
     
         3 . The method of  claim 1  wherein an increased level of expression of the at least one gene compared to the level of expression of the at least one gene in normal tissue is indicative of a poor prognosis for the subject. 
     
     
         4 . The method of any one of  claims 1  wherein the subject is a human subject. 
     
     
         5 . The method of  claim 4  wherein the at least one gene is selected from the group consisting of NOTCH 1, NOTCH 3 and JAG 1. 
     
     
         6 . The method of  claim 4  wherein the levels of expression of NOTCH I and JAG 1 are determined. 
     
     
         7 . The method of  claim 4  wherein the levels of expression of NOTCH 3 and JAG 1 are determined. 
     
     
         8 . The method of  claim 4  wherein the levels of expression of NOTCH 1 and NOTCH 3 are determined. 
     
     
         9 - 11 . (canceled) 
     
     
         12 . The method of any one of  claims 1  wherein the level of gene expression is determined by a nucleic-acid based assay or by an expressed protein-based assay. 
     
     
         13 - 15 . (canceled) 
     
     
         16 . A method of diagnosing breast cancer in a subject comprising determining the level of expression of at least one Notch receptor gene, Notch ligand gene or Notch signaling target gene in a breast tissue sample obtained from the subject. 
     
     
         17 . The method of  claim 16  comprising determining the level of expression of at least one gene selected from the group consisting of Notch 1, Notch 3, Jagged 1, Hey 1, Hey 2, HeyL, Hes 1, Hes 2, Hes 3, Hes 4, Hes 5, Hes 6 and Hes 7. 
     
     
         18 . The method of  claim 16  wherein an increased level of expression of the at least one gene compared to the level of expression of the at least one gene in normal breast tissue is indicative of breast cancer in the subject. 
     
     
         19 . The method of any one of  claims 16  wherein the subject is a human subject. 
     
     
         20 . The method of  claim 19  wherein the at least one gene is selected from the group consisting of NOTCH 1, NOTCH 3 and JAG 1. 
     
     
         21 . The method of  claim 19  wherein the levels of expression of NOTCH 1 and JAG 1 are determined. 
     
     
         22 . The method of  claim 19  wherein the levels of expression of NOTCH 3 and JAG 1 are determined. 
     
     
         23 . The method of  claim 19  wherein the levels of expression of NOTCH 1 and NOTCH 3 are determined. 
     
     
         24 - 26 . (canceled) 
     
     
         27 . The method of any one of  claims 16  wherein the level of gene expression is determined by a nucleic-acid based assay or by an expressed protein-based assay. 
     
     
         28 - 30 . (canceled) 
     
     
         31 . A method for treating a subject suffering from a breast tumor associated with increased Notch signaling comprising administering to the subject an effective amount of an inhibitor of Notch signaling. 
     
     
         32 . The method of  claim 31  wherein the inhibitor of Notch signaling reduces expression of at least one gene selected from the group consisting of Notch 1, Notch 3, Jagged 1. Hey 1, Hey 2, HevL and Hes 1 to Hes 7. 
     
     
         33 . The method of  claim 31  wherein the inhibitor of Notch signaling reduces the activity of at least one protein selected from the group consisting of Notch 1, Notch 3, Jagged 1, Hey 1, Hey 2, HeyL and Hes 1 to Hes 7. 
     
     
         34 . The method of  claim 32  wherein the inhibitor of Notch signaling is one or more antisense oligonucleotides or siRNAs which hybridise to the at least one gene or a complementary sequence thereof. 
     
     
         35 . The method of  claim 33  wherein the inhibitor of Notch signaling is a γ˜secretase inhibitor. 
     
     
         36 . The method of any one of  claims 31  wherein the subject is human and wherein the inhibitor of Notch signaling reduces expression of at least one of NOTCH 1, NOTCH 3 and JAG 1. 
     
     
         37 - 48 . (canceled) 
     
     
         49 . A method for screening a candidate compound for its potential usefulness in the treatment of breast cancer comprising contacting a cell or cells with the candidate compound under conditions which permit expression in the cell(s) of at least one gene selected from the group consisting of Notch I, Notch 3, Jagged 1 Hey 1, Hey 2, HevL and Hes 1 to Hes 7 and determining the level of expression of said at least one gene in the cell(s), wherein a lower level of expression compared to the level of expression in the cell or cells in the absence of the compound indicates the potential usefulness of the compound in the treatment of breast cancer.